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Synthesis and Anticonvulsant Activity of 6‐Alkoxy‐[1,2,4]Triazolo[3,4‐ a ]Phthalazines
Author(s) -
Zhang Lei,
Guan LiPing,
Sun XianYu,
Wei ChengXi,
Chai KyuYun,
Quan ZheShan
Publication year - 2009
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/j.1747-0285.2009.00776.x
Subject(s) - phthalazine , chemistry , anticonvulsant , neurotoxicity , alkoxy group , pharmacology , medicinal chemistry , toxicity , organic chemistry , epilepsy , medicine , alkyl , psychiatry
A new series of 6‐alkoxy‐[1,2,4]triazolo[3,4‐ a ]phthalazines ( 3a – 3v ) were synthesized and their anticonvulsant activity and neurotoxicity were evaluated by the maximal electroshock test and the rotarod test respectively. Significant anticonvulsant activity was displayed by a number of compounds. The most promising compounds 6‐(4‐chlorobenzyloxy)‐[1,2,4]triazolo[3,4‐ a ]phthalazine ( 3f) and 6‐heptyloxy‐[1,2,4]triazolo[3,4‐ a ]phthalazine ( 3s) showed a median effective dose of 7.1 and 11.0 mg/kg, and had protective index value of 5.2 and 8.0 respectively. The two compounds were further found to have potent activity against seizures induced by pentylenetetrazole, isoniazid, thiosemicarbazide, 3‐mercaptopropionic acid but not seizures induced by strychnine, indicating that the two compounds might function by enhancing gamma‐aminobutyric acid neurotransmission.